CDK2 activity determines the timing of cell-cycle commitment and sequential DNA replication
Kim, S.; Leong, A.; Nayar, C.; Kim, M.; Yang, H. W.
Show abstract
To enter the cell cycle, mammalian cells must cross a point of no return (the commitment point), after which they proceed through the cell cycle regardless of changes in external signaling. This process is tightly regulated by the cyclin-dependent kinases (CDKs) and downstream molecules such as retinoblastoma (Rb). Here we show that CDK2 activity coordinates the timing of cell-cycle commitment and DNA replication. CDK4/6 activation initiates Rb phosphorylation and E2F activity, causing a gradual increase in CDK2 activity. Once CDK2 activity reaches a threshold level, CDK2 triggers the commitment point by maintaining Rb phosphorylation and subsequently initiates DNA replication. While the timing of the commitment point is tightly coupled with DNA replication, our experiments, which acutely increased CDK2 activity, suggest that the timing of the commitment point is before DNA replication. These findings highlight how cells utilize a safety mechanism to maintain genome stability by protecting against incomplete DNA replication.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Time-resolved single-cell sequencing identifies multiple waves of mRNA decay during mitotic exit 97%
- Oversized cells activate global proteasome-mediated protein degradation to maintain cell size homeostasis 97%
- Genome-Wide CRISPR Screen Identifies Non-Canonical NF-κB Signaling as a Potent Regulator of Density-dependent Proliferation 96%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Signaling by the integrated stress response kinase PKR is fine-tuned by dynamic clustering 96%
- Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase to ensure proper centriole duplication cycle 96%
- Nucleocytoplasmic transport rates are regulated by cellular processes that modulate GTP availability 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.